The Experts below are selected from a list of 24675 Experts worldwide ranked by ideXlab platform
D. S. Mcqueen - One of the best experts on this subject based on the ideXlab platform.
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Tonic activity of rat medial vestibular nucleus neurones in vitro and its inhibition by GABA
Experimental Brain Research, 1992Co-Authors: M. B. Dutia, A. R. Johnston, D. S. McqueenAbstract:The spontaneous discharge of 48 medial vestibular nucleus (MVN) neurones was recorded extracellularly in horizontal slices of the rat brainstem in vitro. The mean tonic rate of discharge was 17.1±8.2 imp/s, similar to that observed by others in transverse (coronal) slices of the rat and guinea pig MVN. The tonic rate of discharge of individual MVN cells either increased or decreased after synaptic blockade in low Ca^2+ media, suggesting that ongoing synaptic activity has an important influence on the spontaneous activity of MVN cells in vitro. However the persistence of tonic activity after synaptic blockade indicates that an intrinsic, pacemaker-like mechanism is involved in the generation of the tonic activity. GABA, muscimol, Baclofen and 3-APA inhibited the tonic activity of all MVN cells tested. Bicuculline antagonised, and picrotoxin blocked, the inhibitory responses to muscimol, but the effects of GABA were only partially blocked in 50 μ M picrotoxin. The effects of Baclofen and 3-APA persisted in low Ca^2+ media, and were antagonised by saclofen and phaclofen. Picrotoxin-resistant responses to GABA persisted in low Ca^2+ media, and were also antagonised by saclofen. These results suggest that the inhibitory control of MVN neurones by GABA involves both the GABA_A and GABA_B subtypes of GABA receptor. GABA_B receptors appear to be distributed both pre- and post-synaptically in the rat MVN. The possible significance of the intrinsic, tonic activity of MVN cells in normal vestibular function and in vestibular compensation, and the effects of GABA, are discussed.
Klaus Ballanyi - One of the best experts on this subject based on the ideXlab platform.
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Synaptic inhibition in the isolated respiratory network of neonatal rats.
European Journal of Neuroscience, 1998Co-Authors: Johannes Brockhaus, Klaus BallanyiAbstract:Gramicidin-perforated patch-clamp recording revealed phasic Cl(-)-mediated hyperpolarizations in respiratory neurons of the brainstem-spinal cord preparation from newborn rats. The in vitro respiratory rhythm persisted after block of gamma-aminobutyric acid (GABA), i.e. GABAA, receptor-mediated inhibitory postsynaptic potentials (IPSPs) with bicuculline and/or glycinergic IPSPs with strychnine. In one class of expiratory neurons, bicuculline unmasked inspiration-related excitatory postsynaptic potentials (EPSPs), leading to spike discharge. Bicuculline also blocked hyperpolarizations and respiratory arrest due to bath-applied muscimol, whereas strychnine antagonized similar responses to glycine. The reversal potential of respiration-related IPSPs and responses to GABA, muscimol or glycine was not affected by CO2/HCO3(-)-free solutions, but shifted from about -65 mV to values more positive than -20 mV upon dialysis of the cells with 144 instead of 4 mM Cl-. Impairment of GABA uptake with nipecotic acid or glycine uptake with sarcosine evoked a bicuculline- or strychnine-sensitive decrease of respiratory frequency which could lead to respiratory arrest. Also, the GABAB receptor agonist Baclofen led to reversible suppression of respiratory rhythm. This in vitro apnoea was accompanied by a K+ channel-mediated hyperpolarization (reversal potential -88 mV) of tonic cells, whereas membrane potential of neighbouring respiratory neurons remained almost unaffected. Both Baclofen-induced hyperpolarization and respiratory depression were antagonised by 2-OH-saclofen, which did not affect respiration-related IPSPs per se. The results show that synaptic inhibition is not essential for rhythmogenesis in the isolated neonatal respiratory network, although (endogenous) GABA and glycine have a strong modulatory action. Hyperpolarizing IPSPs mediated by GABAA and glycine receptors provide a characteristic pattern of membrane potential oscillations in respiratory neurons, whereas GABAB receptors rather appear to be a feature of non-respiratory neurons, possibly providing excitatory drive to the network.
Monique Denavit-saubié - One of the best experts on this subject based on the ideXlab platform.
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Effects of GABAB receptor agonists and antagonists on the bulbar respiratory network in cat
Brain Research, 1993Co-Authors: Olivier Pierrefiche, Arthur S. Foutz, Monique Denavit-saubiéAbstract:Abstract We examined the involvement of the GABAB receptor in central respiratory mechanisms. Respiratory neurons (RNs) from the ventral respiratory group in the medulla of the cat were subjected to iontophoretic applications of the GABAB receptor agonist Baclofen and the antagonists saclofen and CGP 35348.In all types of RNs Baclofen decreased the firing rate. This reduction was antagonized by CGP 35348. Application of either antagonist increased the spontaneous discharge in both inspiratory and expiratory RNs. CGP 35348 excited 57% of the neurons tested, on the average by 34% with ejection currents of 100 nA. Saclofen excited 6 of 9 neurons tested. Baclofen administered systemically (8–12 mg/kg i.v.) to either anesthetized, decerebrate or intact freely moving cats, induced a selective lengthening of the inspiratory phase, an effect comparable to the apneusis induced by the NMDA antagonist MK-801. Baclofen also produced either a pronounced decrease in the amplitude of phrenic nerve discharge or an apnea, both of which were reversed by increasing paCO2. The results suggest that endogenously released GABA acting on GABAB receptors may be involved in the control of respiratory neuronal discharge.
James C. Garbutt - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Baclofen for alcohol dependence a randomized double blind placebo controlled trial
Alcoholism: Clinical and Experimental Research, 2010Co-Authors: James C. Garbutt, Alexei B Kampovpolevoy, Robert Gallop, Linda Kalkajuhl, Barbara FlanneryAbstract:Background: Recent clinical trials and case-reports indicate that Baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with Baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of Baclofen in alcohol dependence in the United States. Methods: The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of Baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined. Results: Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for Baclofen during treatment (t73 = 0.59, p = 0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F1,73 = 5.39, p = 0.02). Baclofen was well tolerated with only 2 individuals stopping Baclofen because of adverse events. There were no serious adverse events. Conclusions: Baclofen, a GABAB agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with Baclofen in Italy, the current trial did not find evidence that Baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether Baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.
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Effectiveness and safety of Baclofen in the treatment of alcohol dependent patients.
CNS & neurological disorders drug targets, 2010Co-Authors: Lorenzo Leggio, James C. Garbutt, Giovanni AddoloratoAbstract:Both preclinical and clinical research studies have shown the GABA(B) receptor agonist Baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that Baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, Baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that Baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of Baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients. For example, a recent US trial failed to demonstrate a robust effect of Baclofen in treating alcohol-dependent patients though the relative moderate severity of alcohol-dependence in that trial has been suggested as one factor that may have contributed to the finding. In the present review, the authors will summarize the published clinical studies on the role of Baclofen in alcohol dependence and will also present some unpublished secondary analyses. Finally, the authors will discuss possible future directions to further investigate the role of Baclofen in alcohol dependence (e.g., Baclofen's biobehavioral mechanisms, different Baclofen doses, differences in severity and in alcoholic subtypes, different formulations of Baclofen, possible combination of Baclofen with other medications).
Frederic Gagnadoux - One of the best experts on this subject based on the ideXlab platform.
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severe central sleep apnea associated with chronic Baclofen therapy a case series
Chest, 2016Co-Authors: Pierreyves Olivier, Marie Joyeuxfaure, T Gentina, Sandrine Launois, M P Dortho, Jeanlouis Pepin, Frederic GagnadouxAbstract:Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, Baclofen has been shown to decrease respiratory drive. In humans, however, use of Baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of Baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic Baclofen therapy for alcohol withdrawal. In one patient, Baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with Baclofen. Given the increasing number of patients receiving Baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with Baclofen usage.